Because
of the role that papillomavirus plays in causing cervical and other types of
cancer, there has been a lot of research into the development of a vaccine
against some strains of HPV. HPV-16 is present in 50 percent of cervical
cancers and high-grade cervical intraepithelial neoplasias, and in 25 percent
of low-grade intraepithelial neoplasias. Theoretically, a preventative vaccine
could drastically reduce the prevalence of cervical cancer by reducing the
number of individuals infected with HPV. Although primary prevention of all HPV
infections may be impossible to achieve, secondary prevention (elimination of
low-grade lesions before they progress to invasive cancer) is a more realistic
goal. Among the hurdles yet to be overcome are the type-specificity of
neutralizing antibodies (current vaccine formulas that generate immunity to
HPV-16 will be less effective against other oncogenic HPV types) and the lack
of a rapid, inexpensive serologic test to identify incident infections.
However, progress in the field has been exceptionally rapid, and motivation is
high. The majority of current cervical cancer deaths occur in developing
countries that lack the resources for widespread cytologic screening through
Pap smears. Thus, the potential public health benefit of an effective HPV
vaccine would be hard to overstate.

http://www.ranzcog.edu.au/Open/front-page/hpv-vaccine-study.htm

In
a study published in the New England Journal of Medicine in November of 2002,
the results from a multi-center, randomized clinical trial of a preventative
vaccine against HPV 16 were reported and proved very promising. Over 2000 women
from the ages of 16 to 23 who were not infected with HPV 16 were given three
doses of a placebo or HPV-16 virus-like-particle vaccine at day 0, month 2, and
month 6. They were then followed for almost a year and a half to determine the
incidence of HPV 16. The incidence of persistent HPV-16 infection was 3.8 per
100 women-years at risk in the placebo group and 0 per 100 women-years at risk
in the vaccine group. In other words, the vaccine was 100% efficacious. In
addition, the only cases of cervical intraepithelial neoplasia that were found
occurred among the placebo recipients. This reduction in HPV-16-related
cervical intraepithelial neoplasia may eventually reduce the incidence of
cervical cancer.

Merck
currently has a quadrivalent HPV vaccine, which protects against HPV 6, 11, 16,
and 18, in phase III clinical trials. 16 and 18 are the two most common
cancer-causing strains, while 6 and 11 are most commonly associated with
genital warts. Interestingly, while including 6 and 11 in the vaccine increases
the duration of clinical trials, they are necessary to include because people
are more likely to be vaccinated in order to receive visible results,
especially in the case of men, who cannot develop cervical cancer.

The results from these trials are very promising
thus far. None of the women who received the vaccine have contracted HPV. The
trials will continue to follow these women to see if the initial protection
offered by the vaccine has long-term potential. Limitations of this vaccine
include that it only protect against four strains of HPV. It also is not a
therapeutic vaccine; that is, it does not prevent against a person who is
already infected with HPV from developing HPV-related cancer. Finally, it is
not yet known how long the immunity will last.

Research into the development of a therapeutic
vaccine is also ongoing. A new study, published in Cancer Immunology and
Immunotherapy, reported on the results from a phase I/II trial of the effectiveness
of a HPV-16 E7 protein-based vaccine in women with oncogenic HPV-positive
cervical intraepithelial neoplasia. All of the vaccinated patients, but not the
placebo, showed significant immune response to the vaccine, justifying further
analysis of this vaccine. Another study recently published in Virology used a
recombinant Kunjin virus vector with a CTL epitope of HPV 16 E7 protein. This
vector system was shown to be efficacious in inducing protective immunity
against HPV 16 E7-expressing tumors in mice. A third study in the Journal of
Virology tested a therapeutic vaccine in mice that used the HPV 16 E5 protein.

Vaccination against HPV could have incredible
benefits for developing countries, where the screening tests for infection to
prevent cervical cancer are virtually nonexistent. One study looked at the
feasibility of developing an oral vaccine, which would be particularly
beneficial in countries that lack adequate production and delivery
infrastructure for vaccines. The study showed that HPV
L1 proteins can be expressed in genetically engineered plants and that these
proteins elicit an immune response against the viral-like particles that could
possibly provide protective humoral immunity to HPV.

Information on further research into both
therapeutic and prophylactic vaccines can be found in the section on new and hot research.